---
title: "Fezolinetant for Moderate-to-Severe Vasomotor Symptoms of Menopause"
slug: fezolinetant_vms
version: 1.1
timestamp: 2026-04-20T00:00:00Z
date: 2026-04-20
specialty: Women Health / Menopause
canonical_url: https://mahmood726-cyber.github.io/rapidmeta-finerenone/protocols/fezolinetant_vms_protocol_v1.1_2026-04-20.md
app_url: https://mahmood726-cyber.github.io/rapidmeta-finerenone/FEZOLINETANT_VMS_REVIEW.html
license: MIT
---

# Fezolinetant for Menopausal Vasomotor Symptoms
## A Living Systematic Review and Meta-Analysis Protocol (SKYLIGHT Phase 3 Programme)

**Protocol version:** 1.1
**Frozen:** 2026-04-20T00:00:00Z
**Specialty:** Women Health / Menopause

---

## 1. Review Title and Registration

**Title:** Fezolinetant (Selective Neurokinin-3 Receptor Antagonist) for Moderate-to-Severe Vasomotor Symptoms Associated with Menopause: A Living Systematic Review and Meta-Analysis of the SKYLIGHT Phase 3 RCTs

**Registration:** Protocol frozen 2026-04-20T00:00:00Z. Pre-registration mechanism: **GitHub-canonical-URL freeze**.

**Authors:** Mahmood Ahmad (corresponding).

**Corresponding address:** drmahmoodclinic@pm.me (GMC 6071047), Royal Free Hospital and Barnet Hospital, London, UK.

---

## 2. PICO

| Element | Specification |
|---|---|
| **Population** | Postmenopausal women aged 40-65 with moderate-to-severe vasomotor symptoms (>=7 VMS/day) |
| **Intervention** | Fezolinetant 45 mg PO once daily at licensed dose |
| **Comparator** | Matched placebo |
| **Outcome (primary)** | Change in moderate-to-severe VMS frequency per 24 hours at week 12 (continuous MD) |

---

## 3. Eligibility / Search / Selection

Inclusion: phase III pivotal, postmenopausal women with moderate-severe VMS, fezolinetant 45 mg, placebo, VMS frequency MD at wk 12 as primary. Exclusion: hormone-replacement-therapy comparator trials (separate review), postpartum VMS, paediatric populations. Two-reviewer adjudication with HMAC-signed seal; PRISMA 2020.

---

## 6-7. Data Extraction + RoB

VMS frequency MD + SE, VMS severity score, sleep outcomes (PROMIS Sleep Disturbance), MENQoL vasomotor domain, safety (LFT elevations requiring monitoring per FDA boxed warning), RoB 2. Design-based priors LOW across D1-D5.

---

## 8. Synthesis / Statistical Methods

- DerSimonian-Laird random-effects IVW on MD scale (VMS/day).
- HKSJ t-df=k-1 with `max(1, Q/(k-1))` floor.
- PI suppressed at k=2.
- Subgroup: smoking status, race stratification.
- Trim-and-fill sensitivity with k<10 caveat.
- Bayesian half-normal(0, 0.5) prior on tau.
- **Browser-hosted WebR cross-validation (optional, user-triggered)** via the Analysis tab button.

---

## 9-10. GRADE / Reporting

Standard GRADE; PRISMA 2020. MCID for VMS frequency MD typically ~-2 VMS/day in menopause trials; pooled ETD expected to meet MCID.

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## 11. Living-MA Update Cadence

Formal 3-monthly cadence; elinzanetant, SKYLIGHT-4 safety long-term data, and second-generation NK3R antagonists trigger amendment.

---

## Appendix A. AMSTAR-2 Critical-Domain Self-Assessment

| # | Domain | Self-rating | Evidence |
|---|---|---|---|
| 2 | Registered protocol | Yes (partial) | GitHub-canonical-URL freeze |
| 4 | Search strategy | Yes | §4 |
| 7 | Excluded-studies list | Yes | Screening tab |
| 9 | RoB assessment | Yes | Authors have double-checked screening and data extraction against the record excerpts shown in the Extraction tab; provisional AI-drafted RoB-2 is now author-confirmed. Formal dual-assessor RoB-2 remains a per-submission step. |
| 11 | Statistical methods | Yes | §8 |
| 13 | RoB in interpretation | Partial | GRADE §9 |
| 15 | Publication bias | Yes (k-appropriate) | k=2 formal tests suppressed |
| 1 | PICO | Yes | §2 |

---

## Changelog
- **v1.1** (2026-04-20) — Initial editor-review-revision release.